Positions

Overview

  • Dr. Shelton attended medical school at the University of Louisville in Kentucky. He was then a resident and Chief Resident at the Massachusetts Mental Health Center (now the Longwood Program), a teaching hospital of the Harvard Medical School in Boston, MA., followed by a research fellowship at the National Institutes of Mental Health Intramural Program in Washington, D.C. He joined the faculty of Vanderbilt University, where he became the James G. Blakemore Research Professor and Vice Chair for Clinical Research in the Department of Psychiatry. Dr. Shelton joined the faculty of the Department of Psychiatry and Behavioral Neurobiology at the University of Alabama at Birmingham in February 2012 as the Charles Byron Ireland Professor, Vice Chair for Research, and head of the Mood Disorders Program. Dr. Shelton has been an active physician-scientist and educator. He and his colleagues have had more than 120 funded research studies from the NIH, other Federal agencies, foundations, and industry. He has more than 350 publications, comprising original research reports, reviews, commentaries, and book chapters. Dr. Shelton’s research focuses on the development of new ways to treat and prevent depression and suicide.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2019 Analysis of Clinical Trial Exit Interview Data in Patients with Treatment-Resistant DepressionPatient.  12:527-537. 2019
    2019 Complex polypharmacy in bipolar disorder: Side effect burden, adherence, and response predictorsJournal of Affective Disorders.  257:17-22. 2019
    2019 Multi-site investigation of strategies for the clinical implementation of CYP2D6 genotyping to guide drug prescribingGenetics in Medicine.  21:2255-2263. 2019
    2019 A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Adjunctive Pimavanserin in Patients With Major Depressive Disorder and an Inadequate Response to Therapy (CLARITY)Journal of Clinical Psychiatry.  80. 2019
    2019 Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients with Treatment-Resistant Depression: A Randomized Clinical TrialJAMA Psychiatry.  76:893-903. 2019
    2019 Response to: Goldberg et al. and Severance et al. Letters to the Editor: The clinical significance of improving remission over standard of care – The reality of treatment resistant-based therapiesJournal of Psychiatric Research.  114:211-213. 2019
    2019 Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: A randomized double-blind active-controlled studyAmerican Journal of Psychiatry.  176:428-438. 2019
    2019 Patterns of changes in bipolar depressive symptoms revealed by trajectory analysis among 482 patients with bipolar disorderBipolar Disorders.  21:350-360. 2019
    2019 Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: A large, patient- and rater-blinded, randomized, controlled studyJournal of Psychiatric Research.  111:59-67. 2019
    2019 Comorbid anxiety in bipolar CHOICE: Insights from the bipolar inventory of symptoms scaleJournal of Affective Disorders.  246:126-131. 2019
    2019 49 Combinatorial Pharmacogenomics to Guide Treatment Selection for Major Depressive Disorder: A Large, Blinded, Randomized Controlled TrialCNS Spectrums.  24:202-203. 2019
    2019 Correlation between white blood cell count and mood-stabilising treatment response in two bipolar disorder trialsActa Neuropsychiatrica2019
    2019 Effect of race on the relationship between child maltreatment and obesity in Whites and BlacksStress2019
    2019 Serotonin and Norepinephrine Reuptake InhibitorsHandbook of Experimental Pharmacology.  250:145-180. 2019
    2018 Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorderActa Neuropsychiatrica.  30:297-305. 2018
    2018 Decreased activation and subsyndromal manic symptoms predict lower remission rates in bipolar depressionAustralian and New Zealand Journal of Psychiatry.  52:994-1002. 2018
    2018 Treatment outcomes of acute bipolar depressive episode with psychosisDepression and Anxiety.  35:402-410. 2018
    2018 Major Depressive Disorder Following Dermatomyositis: A Case Linking Depression with InflammationPsychopharmacology Bulletin.  48:22-28. 2018
    2018 Role of complex epigenetic switching in tumor necrosis factor-α upregulation in the prefrontal cortex of suicide subjectsAmerican Journal of Psychiatry.  175:262-274. 2018
    2018 Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: A randomized clinical trialJAMA Psychiatry.  75:139-148. 2018
    2018 Corrigendum to bipolar mixed features – Results from the comparative effectiveness for bipolar disorder (Bipolar CHOICE) study [Journal of Affective Disorders 217 (2017) 183–189], (S0165032716323047), (10.1016/j.jad.2017.03.070))Journal of Affective Disorders.  225:775-777. 2018
    2018 Double-blind, proof-of-concept (POC) trial of Low-Field Magnetic Stimulation (LFMS) augmentation of antidepressant therapy in treatment-resistant depression (TRD)Brain Stimulation.  11:75-84. 2018
    2018 Efficacy of ziprasidone augmentation of escitalopram for cognitive symptoms of major depressive disorderJournal of Clinical Psychiatry.  79:55-59. 2018
    2018 Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysisJournal of Affective Disorders.  225:422-428. 2018
    2018 Sleep disturbance may impact treatment outcome in bipolar disorder: A preliminary investigation in the context of a large comparative effectiveness trialJournal of Affective Disorders.  225:563-568. 2018
    2018 The impact of binge eating behavior on lithium- and quetiapine-associated changes in body weight, body mass index, and waist circumference during 6 months of treatment: Findings from the bipolar CHOICE studyJournal of Affective Disorders2018
    2017 Brain structure, function, and neurochemistry in schizophrenia and bipolar disorder- A systematic review of the magnetic resonance neuroimaging literaturenpj Schizophrenia.  3. 2017
    2017 Poor quality of life and functioning in bipolar disorderInternational Journal of Bipolar Disorders.  5. 2017
    2017 Trajectories of suicidal ideation over 6 months among 482 outpatients with bipolar disorderJournal of Affective Disorders.  223:146-152. 2017
    2017 Gender-specific relationship between obesity and major depressionFrontiers in Endocrinology.  8. 2017
    2017 Response to: Commentary: Sex differences in the peripheral immune system in patients with depressionFrontiers in Psychiatry.  8. 2017
    2017 Clinical and genetic predictors of delayed remission after multiple levels of antidepressant treatment: Toward early identification of depressed individuals for advanced care optionsJournal of Clinical Psychiatry.  78:e1291-e1298. 2017
    2017 Bipolar mixed features – Results from the comparative effectiveness for bipolar disorder (Bipolar CHOICE) studyJournal of Affective Disorders.  217:183-189. 2017
    2017 Clinical correlates of acute bipolar depressive episode with psychosisJournal of Affective Disorders.  217:29-33. 2017
    2017 Willingness of Mentally Ill Individuals to Sign Up for a Novel Proposal to Prevent Firearm SuicideSuicide and Life-Threatening Behavior.  47:483-492. 2017
    2017 Sex differences in the peripheral immune system in patients with depressionFrontiers in Psychiatry.  8. 2017
    2017 DNA methylation and expression of stress related genes in PBMC of MDD patients with and without serious suicidal ideationJournal of Psychiatric Research.  89:115-124. 2017
    2017 A pilot trial of In vivo NRT sampling to increase medication adherence in community corrections smokersAddictive Behaviors.  67:92-99. 2017
    2017 White blood cell count correlates with mood symptom severity and specific mood symptoms in bipolar disorderAustralian and New Zealand Journal of Psychiatry.  51:355-365. 2017
    2017 Ziprasidone augmentation of escitalopram for major depressive disorder: Cardiac, endocrine, metabolic, and motoric effects in a randomized, double-blind, placebo-controlled studyJournal of Clinical Psychiatry.  78:449-455. 2017
    2017 Identification of MicroRNA-124-3p as a Putative Epigenetic Signature of Major Depressive DisorderNeuropsychopharmacology.  42:864-875. 2017
    2017 Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol do not affect 6-month mood-stabilizing treatment outcome among 482 patients with bipolar disorderDepression and Anxiety.  34:281-290. 2017
    2016 Depression, Antidepressants, and Weight Gain in ChildrenObesity Research.  24:2450. 2016
    2016 Dimensions of schizophrenia and their time course of response to a second generation antipsychotic olanzapine—A clinical studyAsian Journal of Psychiatry.  24:17-22. 2016
    2016 Psilocybin and palliative end-of-life careJournal of Psychopharmacology.  30:1207-1208. 2016
    2016 Tracking medication changes to assess outcomes in comparative effectiveness research: A bipolar CHOICE studyJournal of Affective Disorders.  205:159-164. 2016
    2016 Ziprasidone augmentation for anxious depressionInternational Clinical Psychopharmacology.  31:341-346. 2016
    2016 A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depressionAmerican Journal of Psychiatry.  173:816-826. 2016
    2016 Specific pharmacological effects of paroxetine comprise psychological but not somatic symptoms of depressionPLoS ONE.  11. 2016
    2016 Notice of Retraction and Replacement. Hollon et al. Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder: A randomized clinical trial. JAMA Psychiatry. 2014;71(10):1157-1164JAMA Psychiatry.  73:639-640. 2016
    2016 An altered peripheral IL6 response in major depressive disorderNeurobiology of Disease.  89:46-54. 2016
    2016 Are placebo-controlled trials of depression safe?Lancet Psychiatry.  3:393-395. 2016
    2016 Long-Term Efficacy, Safety, and Tolerability of l-Methylfolate Calcium 15 mg as Adjunctive Therapy With Selective Serotonin Reuptake Inhibitors: A 12-Month, Open-Label Study Following a Placebo-Controlled Acute StudyJournal of Clinical Psychiatry.  77:654-660. 2016
    2016 Impact of Major Depressive Disorder on Prediabetes by Impairing Insulin Sensitivity.Journal of Diabetes and Metabolism.  7. 2016
    2016 The course of illness after initial diagnosis of major depressionJAMA Psychiatry.  73:321-322. 2016
    2016 A tool to predict suicidal ideation and behavior in bipolar disorder: The Concise Health Risk Tracking Self-ReportJournal of Affective Disorders.  192:212-218. 2016
    2016 Molecular analyses of circadian gene variants reveal sex-dependent links between depression and clocksTranslational Psychiatry.  6. 2016
    2016 A placebo-controlled crossover study of iloperidone augmentation for residual anger and irritability in major depressive disorder.Therapeutic Advances in Psychopharmacology.  6:4-12. 2016
    2016 Baseline disability and poor functioning in Bipolar disorder predict worse outcomes: Results from the Bipolar CHOICE studyJournal of Clinical Psychiatry.  77:100-108. 2016
    2016 Bipolar CHOICE (clinical health outcomes initiative in comparative effectiveness): A pragmatic 6-month trial of lithium versus quetiapine for Bipolar disorderJournal of Clinical Psychiatry.  77:90-99. 2016
    2016 Obesity, but not metabolic syndrome, negatively affects outcome in bipolar disorderActa Psychiatrica Scandinavica.  133:144-153. 2016
    2015 Association of obesity and inflammatory marker levels on treatment outcome: Results from a double-blind, randomized study of adjunctive l-methylfolate calcium in patients with MDD who are inadequate responders to SSRIsJournal of Clinical Psychiatry.  76:1635-1641. 2015
    2015 Ziprasidone augmentation of escitalopram for major depressive disorder: Efficacy results from a randomized, Double-Blind, Placebo-Controlled StudyAmerican Journal of Psychiatry.  172:1251-1258. 2015
    2015 The pro-inflammatory profile of depressed patients is (partly) related to obesityJournal of Psychiatric Research.  70:91-97. 2015
    2015 Childhood maltreatment increases the risk for visceral obesityObesity Research.  23:1625-1632. 2015
    2015 Psychotherapy use in bipolar disorder: Association with functioning and illness severityAustralian and New Zealand Journal of Psychiatry.  49:453-461. 2015
    2015 Medical burden in bipolar disorder: Findings from the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE)Bipolar Disorders.  17:212-223. 2015
    2015 Coordinated messenger RNA/microRNA changes in fibroblasts of patients with major depressionBiological Psychiatry.  77:256-265. 2015
    2015 Assessment of the Efficacy and Safety of BMS-820836 in Patients with Treatment-Resistant Major Depression: Results from 2 Randomized, Double-Blind StudiesJournal of Clinical Psychopharmacology.  35:454-459. 2015
    2015 Complexity of illness and adjunctive benzodiazepine use in outpatients with bipolar i or II disorder results from the bipolar CHOICE studyJournal of Clinical Psychopharmacology.  35:68-74. 2015
    2015 Fibroblasts from patients with major depressive disorder show distinct transcriptional response to metabolic stressorsTranslational Psychiatry.  5. 2015
    2015 Gains in employment status following antidepressant medication or cognitive therapy for depressionBritish Journal of Psychiatry.  206:332-338. 2015
    2015 MDDScore: Confirmation of a blood test to aid in the diagnosis of major depressive disorderJournal of Clinical Psychiatry.  76:e199-e206. 2015
    2015 Reply to commentary by rothschild: "A blood test for depression?"Journal of Clinical Psychiatry.  76:e1038. 2015
    2015 What are the comparative benefits and harms of augmentation treatments in major depression?Journal of Clinical Psychiatry.  76:e531-e533. 2015
    2014 Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder a randomized clinical trialJAMA Psychiatry.  71:1157-1164. 2014
    2014 Erratum: "Effect of adjunctive benzodiazepines on clinical outcomes in lithium- or quetiapine-treated outpatients with bipolar i or II disorder: Results from the bipolar CHOICE trial" [Journal of Affective Disorders (2014) 161 (30-35)]Journal of Affective Disorders.  167:259-260. 2014
    2014 Posttraumatic stress disorder after high-dose-rate brachytherapy for cervical cancer: In regard to Kirchheiner et alInternational Journal of Radiation Oncology - Biology - Physics.  90:468. 2014
    2014 Effect of adjunctive benzodiazepines on clinical outcomes in lithium- or quetiapine-treated outpatients with bipolar i or II disorder: Results from the Bipolar CHOICE trialJournal of Affective Disorders.  161:30-35. 2014
    2014 Antidepressants and suicide attempts in childrenPediatrics.  133:204-210. 2014
    2014 Clinical and health outcomes initiative in comparative effectiveness for bipolar disorder (Bipolar CHOICE): A pragmatic trial of complex treatment for a complex disorderClinical Trials.  11:114-127. 2014
    2014 The effect of regulatory advisories on maternal antidepressant prescribing, 1995-2007: An interrupted time series study of 228,876 pregnanciesArchives of Women's Mental Health.  17:17-26. 2014
    2014 Metabolic stress-induced microRNA and mRNA expression profiles of human fibroblastsExperimental Cell Research.  320:343-353. 2014
    2014 BDNF, interleukin-6, and salivary cortisol levels in depressed patients treated with desvenlafaxineProgress in Neuro-Psychopharmacology and Biological Psychiatry.  48:86-91. 2014
    2014 Early life trauma and directional brain connectivity within major depressionHuman Brain Mapping.  35:4815-4826. 2014
    2014 Rapid Follow-Up for Patients After Psychiatric CrisisCommunity Mental Health Journal.  51:139-144. 2014
    2013 Association of exercise with quality of life and mood symptoms in a comparative effectiveness study of bipolar disorderJournal of Affective Disorders.  151:722-727. 2013
    2013 Assessing effects of L-methylfolate in depression management: Results of a real-world patient experience trialPrimary Care Companion to the Journal Clinical Psychiatry.  15. 2013
    2013 Identifying suicidal behavior among adolescents using administrative claims dataPharmacoepidemiology and Drug Safety.  22:769-775. 2013
    2013 Increasing use of atypical antipsychotics and anticonvulsants during pregnancyPharmacoepidemiology and Drug Safety.  22:794-801. 2013
    2013 Treatment resistant depression: Strategies for primary care topical collection on psychiatry in primary careCurrent Psychiatry Reports.  15. 2013
    2013 Erratum: Maternal antidepressant use and adverse outcomes: A cohort study of 228,876 pregnancies (American Journal of Obstetrics and Gynecology (2012) 207 49 (e1-9))American Journal of Obstetrics and Gynecology.  208:326. 2013
    2013 Assessment of a multi-assay, serum-based biological diagnostic test for major depressive disorder: A Pilot and Replication StudyMolecular Psychiatry.  18:332-339. 2013
    2013 Convergence and divergence in the delivery of cognitive therapy intwo randomized clinical trialsBehaviour Research and Therapy.  51:493-498. 2013
    2013 Differential change in specific depressive symptoms during antidepressant medication or cognitive therapyBehaviour Research and Therapy.  51:392-398. 2013
    2013 Mitochondrial modulators for bipolar disorder: A pathophysiologically informed paradigm for new drug developmentAustralian and New Zealand Journal of Psychiatry.  47:26-42. 2013
    2013 Reliability and validity of the Symptoms of Depression Questionnaire (SDQ)CNS Spectrums.  19:535-546. 2013
    2012 L-methylfolate as adjunctive therapy for SSRI-resistant major depression: Results of two randomized, double-blind,,parallel-sequential trialsAmerican Journal of Psychiatry.  169:1267-1274. 2012
    2012 Does concomitant use of NSAIDs reduce the effectiveness of antidepressants?American Journal of Psychiatry.  169:1012-1015. 2012
    2012 Predictors of patient cognitive therapy skills and symptom change in two randomized clinical trials: The role of therapist adherence and the therapeutic allianceJournal of Consulting and Clinical Psychology.  80:373-381. 2012
    2012 Depression in patients with head and neck cancer and a functional genetic polymorphism of the serotonin transporter geneHead & neck surgery.  34:359-364. 2012
    2012 A 12-week, randomized, double-blind, placebo-controlled, sequential parallel comparison trial of ziprasidone as monotherapy for major depressive disorderJournal of Clinical Psychiatry.  73:1541-1547. 2012
    2012 Effort-based decision-making in major depressive disorder: A translational model of motivational anhedoniaJournal of Abnormal Psychology.  121:553-558. 2012
    2012 Maternal antidepressant use and adverse outcomes: A cohort study of 228,876 pregnanciesAmerican Journal of Obstetrics and Gynecology.  207:49.e1-49.e9. 2012
    2012 Oxidative stress and glutathione response in tissue cultures from persons with major depressionJournal of Psychiatric Research.  46:1326-1332. 2012
    2012 Review of pharmacological treatment in mood disorders and future directions for drug developmentNeuropsychopharmacology.  37:77-101. 2012
    2011 A Randomized open comparison of long-acting injectable risperidone and treatment as usual for prevention of relapse, rehospitalization, and urgent care referral in community-treated patients with rapid cycling bipolar disorderClinical Neuropharmacology.  34:224-233. 2011
    2011 Functional biomarkers of depression: Diagnosis, treatment, and pathophysiologyNeuropsychopharmacology.  36:2375-2394. 2011
    2011 Inflammation in depression: Is adiposity a cause?Dialogues in Clinical Neuroscience.  13:41-54. 2011
    2011 Agomelatine for the treatment of major depressive disorderExpert Opinion on Pharmacotherapy.  12:2411-2419. 2011
    2011 Randomized comparison of selective serotonin reuptake inhibitor (escitalopram) monotherapy and antidepressant combination pharmacotherapy for major depressive disorder with melancholic features: A CO-MED reportJournal of Affective Disorders.  133:467-476. 2011
    2011 Sustained amygdala response to both novel and newly familiar faces characterizes inhibited temperamentSocial Cognitive and Affective Neuroscience.  6:621-629. 2011
    2011 Suicidal behavior differs among early and late adolescents treated with antidepressant agentsPediatrics.  128:447-454. 2011
    2011 Effects of orally disintegrating vs regular olanzapine tablets on body weight, eating behavior, glycemic and lipid indices, and gastrointestinal hormones: A randomized, open comparison in outpatients with bipolar depressionAnnals of Clinical Psychiatry.  23:193-201. 2011
    2011 Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depressionMolecular Psychiatry.  16:751-762. 2011
    2011 Combining Medications to Enhance Depression Outcomes (CO-MED): Acute and long-term outcomes of a single-blind randomized studyAmerican Journal of Psychiatry.  168:689-701. 2011
    2011 Using moderator-based algorithms and electronic medical records to achieve optimal outcomes in depression.Journal of Clinical Psychiatry.  72. 2011
    2011 Two aspects of the therapeutic alliance: Differential relations with depressive symptom changeJournal of Consulting and Clinical Psychology.  79:279-283. 2011
    2011 Challenges and algorithm-guided treatment in major depressive disorder.Journal of Clinical Psychiatry.  72. 2011
    2011 Crisis of confidence: antidepressant risk versus benefit.Journal of Clinical Psychiatry.  72. 2011
    2011 The relationship between adverse events during selective serotonin reuptake inhibitor treatment for major depressive disorder and nonremission in the suicide assessment methodology studyJournal of Clinical Psychopharmacology.  31:31-38. 2011
    2011 A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depressionJournal of Clinical Psychiatry.  72:1405-1412. 2011
    2011 Childhood trauma history differentiates amygdala response to sad faces within MDDJournal of Psychiatric Research.  45:886-895. 2011
    2011 Evidence for the use of l-methylfolate combined with antidepressants in MDD.Journal of Clinical Psychiatry.  72. 2011
    2011 Moderators of antidepressant response in major depression.Journal of Clinical Psychiatry.  72. 2011
    2011 Performance improvement CME: algorithms and EMRs in depression.Journal of Clinical Psychiatry.  72. 2011
    2011 Using algorithms and computerized decision support systems to treat major depression.Journal of Clinical Psychiatry.  72. 2011
    2010 Biological activities of 7-dehydrocholesterol-derived oxysterols: Implications for Smith-Lemli-Opitz syndromeJournal of Lipid Research.  51:3259-3269. 2010
    2010 Psychosocial outcomes in patients with recurrent major depressive disorder during 2 years of maintenance treatment with venlafaxine extended releaseJournal of Affective Disorders.  126:420-429. 2010
    2010 Risperidone long-acting injectable (Risperdal Consta®) for maintenance treatment in patients with bipolar disorderExpert Review of Neurotherapeutics.  10:1637-1658. 2010
    2010 Can pharmacotherapists be too supportive? A process study of active medication and placebo in the treatment of depressionPsychological Medicine.  40:1379-1387. 2010
    2010 Efficacy, safety and tolerability of Symbyax® for acute-phase management of treatment-resistant depressionExpert Review of Neurotherapeutics.  10:651-670. 2010
    2010 Depressive realism and clinical depressionBehaviour Research and Therapy.  48:257-265. 2010
    2010 Olanzapine monotherapy for acute depression in patients with bipolar I or II disorder: Results of an 8-week open label trialHuman Psychopharmacology: Clinical and Experimental.  25:30-36. 2010
    2010 Therapeutic options for treatment-resistant depressionCNS Drugs.  24:131-161. 2010
    2010 Antidepressant drug effects and depression severity: A patient-level meta-analysisJournal of the American Medical Association.  303:47-53. 2010
    2010 Acute bipolar depression: A review of the use of olanzapine/fluoxetineClinical Medicine Insights : Therapeutics.  2:825-840. 2010
    2010 Converting from brand-name to generic clozapine: A review of effectiveness and tolerability dataAmerican Journal of Health-System Pharmacy.  67:27-37. 2010
    2010 Eating ourselves to death (and despair): The contribution of adiposity and inflammation to depressionProgress in Neurobiology.  91:275-299. 2010
    2009 St John's wort (Hypericum perforatum) in major depressionJournal of Clinical Psychiatry.  70:23-27. 2009
    2009 Long-term management of depression: Tips for adjusting the treatment plan as the patient's needs changeJournal of Clinical Psychiatry.  70:32-37. 2009
    2009 Amygdala temporal dynamics: Temperamental differences in the timing of amygdala response to familiar and novel facesBMC Neuroscience.  10. 2009
    2009 Effectiveness study of venlafaxine-XR combined with aripiprazole for chronic or recurrent major depressive disorderAustralian and New Zealand Journal of Psychiatry.  43:956-967. 2009
    2009 Assessing rates and predictors of tachyphylaxis during the prevention of recurrent episodes of depression with venlafaxine ER for two years (PREVENT) studyPsychopharmacology Bulletin.  42:5-20. 2009
    2009 Personality change during depression treatment: A placebo-controlled trialArchives of General Psychiatry.  66:1322-1330. 2009
    2009 Olanzapine and fluoxetine combination therapy for treatment-resistant depression: Review of efficacy, safety, and study design issuesNeuropsychiatric Disease and Treatment.  5:369-383. 2009
    2009 Protein kinases A and C in post-mortem prefrontal cortex from persons with major depression and normal controlsInternational Journal of Neuropsychopharmacology.  12:1223-1232. 2009
    2009 Fluoxetine and olanzapine combination therapy in treatment-resistant major depression: Review of efficacy and safety dataExpert Opinion on Pharmacotherapy.  10:2145-2159. 2009
    2009 Prediction of Response to Medication and Cognitive Therapy in the Treatment of Moderate to Severe DepressionJournal of Consulting and Clinical Psychology.  77:775-787. 2009
    2009 Symbyax ® (olanzapine and fluoxetine HCl) for the acute treatment of treatment-resistant depressionThe Psychiatric times.  26:20-27. 2009
    2009 Treatment-resistant depression: Understanding its nature and the burden of careThe Psychiatric times.  26:3-7. 2009
    2009 Early adverse events, HPA activity and rostral anterior cingulate volume in MDDPLoS ONE.  4. 2009
    2009 Elevated 5-HT 2A receptors in postmortem prefrontal cortex in major depression is associated with reduced activity of protein kinase ANeuroscience.  158:1406-1415. 2009
    2009 Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxineJournal of Psychiatric Research.  43:247-254. 2009
    2009 Factors associated with concomitant psychotropic drug use in the treatment of major depression: A STAR*D reportCNS Spectrums.  14:487-498. 2009
    2009 Psychiatric profile and attention deficits in postural tachycardia syndromeJournal of Neurology, Neurosurgery and Psychiatry.  80:339-344. 2009
    2009 The role of L-methylfolate in depressive disorders: commentary.CNS Spectrums.  14:8. 2009
    2009 The role of residual symptoms in nonadherence to treatment.CNS Spectrums.  14:3-5. 2009
    2008 Adjunctive use of modafinil in bipolar patients: Just another stimulant or not?Current Psychiatry Reports.  10:520-524. 2008
    2008 Use of atypical antipsychotics for treatment-resistant major depressive disorderCurrent Psychiatry Reports.  10:481-486. 2008
    2008 Sequence of improvement in depressive symptoms across cognitive therapy and pharmacotherapyJournal of Affective Disorders.  110:161-166. 2008
    2008 Multivariate permutation analysis associates multiple polymorphisms with subphenotypes of major depressionGenes, Brain and Behavior.  7:487-495. 2008
    2008 Augmentation of antidepressants with atypical antipsychotics for treatment-resistant major depressive disorderActa Psychiatrica Scandinavica.  117:253-259. 2008
    2008 Antidepressant medications v. cognitive therapy in people with depression with or without personality disorderBritish Journal of Psychiatry.  192:124-129. 2008
    2008 The history and current state of antidepressant clinical trial design: A call to action for proof-of-concept studiesJournal of Clinical Psychiatry.  69:1513-1528. 2008
    2007 The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) Study: Outcomes from the Acute and Continuation PhasesBiological Psychiatry.  62:1371-1379. 2007
    2007 Are Antidepressant Drugs That Combine Serotonergic and Noradrenergic Mechanisms of Action More Effective Than the Selective Serotonin Reuptake Inhibitors in Treating Major Depressive Disorder? A Meta-analysis of Studies of Newer AgentsBiological Psychiatry.  62:1217-1227. 2007
    2007 Evidence for the efficacy of duloxetine in treating mild, moderate, and severe depressionInternational Clinical Psychopharmacology.  22:348-355. 2007
    2007 Augmentation strategies to increase antidepressant efficacyJournal of Clinical Psychiatry.  68:18-22. 2007
    2007 Dr. Shelton replies [4]Journal of Clinical Psychiatry.  68:1619. 2007
    2007 The Relation of Patients' Treatment Preferences to Outcome in a Randomized Clinical TrialBehavior Therapy.  38:209-217. 2007
    2007 The neurobiology of treatment-resistant depressionThe Psychiatric times.  24:25-27. 2007
    2007 Changes in patients' beliefs about the causes of their depression following successful treatmentCognitive Therapy and Research.  31:437-449. 2007
    2007 Patterns of depressive symptom response in duloxetine-treated outpatients with mild, moderate or more severe depressionInternational Journal of Clinical Practice.  61:1337-1348. 2007
    2007 The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study: Outcomes from the 2-year and combined maintenance phasesJournal of Clinical Psychiatry.  68:1246-1256. 2007
    2007 Efficacy and tolerability of adjunctive ziprasidone in treatment-resistant depression: A randomized, open-label, pilot studyJournal of Clinical Psychiatry.  68:1071-1077. 2007
    2007 Issues related to adherence in the treatment of depressionPrimary Psychiatry.  14:42-46. 2007
    2007 Sudden Gains in Cognitive Therapy of Depression and Depression Relapse/RecurrenceJournal of Consulting and Clinical Psychology.  75:404-408. 2007
    2007 Progressive Resistance to a Selective Serotonin Reuptake Inhibitor but Not to Cognitive Therapy in the Treatment of Major DepressionJournal of Consulting and Clinical Psychology.  75:267-276. 2007
    2007 Comparison of quality of life measures in a depressed populationJournal of Nervous and Mental Disease.  195:219-225. 2007
    2007 The Molecular Neurobiology of DepressionPsychiatric Clinics of North America.  30:1-11. 2007
    2007 A randomized, double-blind, crossover trial of modafinil on moodJournal of Clinical Psychopharmacology.  27:76-79. 2007
    2007 Randomized, double-blind, placebo-controlled crossover trials of venlafaxine for hot flashes after breast cancerOncologist.  12:124-135. 2007
    2007 Polymorphisms in the Regulatory Region of the Human Serotonin 5-HT2A Receptor Gene (HTR2A) Influence Gene ExpressionBiological Psychiatry.  61:167-173. 2007
    2007 Are depressed outpatients with and without a family history of substance use disorder different? A baseline analysis of the STAR*D cohortJournal of Clinical Psychiatry.  68:1931-1938. 2007
    2007 Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: A meta-analysisJournal of Clinical Psychiatry.  68:826-831. 2007
    2007 Case Studies in Bipolar Depression: Best Practices for the OutpatientCNS Spectrums.  12:4-13. 2007
    2007 Prevention of recurrent episodes of depression with venlafaxine ER in a 1-year maintenance phase from the PREVENT studyJournal of Clinical Psychiatry.  68:1014-1023. 2007
    2006 Use of treatment algorithms for depressionJournal of Clinical Psychiatry.  67:1458-1465. 2006
    2006 Praise for a critical perspectiveBehavioral and Brain Sciences.  29:405-405. 2006
    2006 The return of fixed combinations in psychiatry: Fluoxetine and olanzapine combinationTherapeutics and Clinical Risk Management.  2:187-192. 2006
    2006 Treatment with venlafaxine extended release after SSRI nonresponse or intolerance: A randomized comparison of standard- and higher-dosing strategiesJournal of Clinical Psychopharmacology.  26:250-258. 2006
    2006 Antidepressant discontinuation syndrome: Consensus panel recommendations for clinical management and additional researchJournal of Clinical Psychiatry.  67:27-30. 2006
    2006 The nature of the discontinuation syndrome associated with antidepressant drugsJournal of Clinical Psychiatry.  67:3-7. 2006
    2006 Norepinephrine transporter-deficient mice respond to anxiety producing and fearful environments with bradycardia and hypotensionNeuroscience.  139:931-946. 2006
    2006 Management of major depressive disorder following failure of first antidepressant treatmentPrimary Psychiatry.  13:73-82. 2006
    2006 Presenting characteristics of depressed outpatients as a function of recurrence: Preliminary findings from the STAR*D clinical trialJournal of Psychiatric Research.  40:59-69. 2006
    2006 A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorderJournal of Clinical Psychiatry.  67:1674-1681. 2006
    2006 Detection of an mRNA polymorphism by differential display.Methods in Molecular Biology.  317:279-285. 2006
    2006 Olanzapine/fluoxetine combination for bipolar depressionExpert Review of Neurotherapeutics.  6:33-39. 2006
    2005 Sequence variation in the human dopamine transporter gene in children with attention deficit hyperactivity disorderNeuropharmacology.  49:724-736. 2005
    2005 Human serotonin transporter variants display altered sensitivity to protein kinase G and p38 mitogen-activated protein kinaseProceedings of the National Academy of Sciences.  102:11545-11550. 2005
    2005 Comorbid psychiatric disorders in depressed outpatients: Demographic and clinical featuresJournal of Affective Disorders.  87:43-55. 2005
    2005 Cognitive therapy vs medications in the treatment of moderate to severe depressionArchives of General Psychiatry.  62:409-416. 2005
    2005 Prevention of relapse following cognitive therapy vs medications in moderate to severe depressionArchives of General Psychiatry.  62:417-422. 2005
    2005 Signal transduction abnormalities in melancholic depressionInternational Journal of Neuropsychopharmacology.  8:5-16. 2005
    2005 Do venlafaxine XR and paroxetine equally influence negative and positive affect?Journal of Affective Disorders.  85:333-339. 2005
    2005 Olanzapine/fluoxetine combination for treatment-resistant depression: A controlled study of SSRI and nortriptyline resistanceJournal of Clinical Psychiatry.  66:1289-1297. 2005
    2005 Treatment of depression in adolescents with cognitive behavior therapy and medications: A commentary on the TADS projectCognitive and Behavioral Practice.  12:149-155. 2005
    2004 Risperidone and paroxetine given singly and in combination for bipolar depressionJournal of Clinical Psychiatry.  65:1715-1719. 2004
    2004 The dual-action hypothesis: Does pharmacology matter?Journal of Clinical Psychiatry.  65:5-10. 2004
    2004 Decreased serotonin 5-HT2A receptor-stimulated phosphoinositide signalling in fibroblasts from melancholic deppresed patientsNeuropsychopharmacology.  29:2081-2087. 2004
    2004 The effectiveness of St. John's wort in major depressive disorder: A naturalistic phase 2 follow-up in which nonresponders were provided alternate medicationJournal of Clinical Psychiatry.  65:1114-1119. 2004
    2004 Early- and late-onset startle modulation in unipolar depressionPsychophysiology.  41:433-440. 2004
    2004 Assessing the effects of bupropion SR on mood dimensions of depressionJournal of Affective Disorders.  78:235-241. 2004
    2004 Differential Expression of Pentraxin 3 in Fibroblasts from Patients with Major DepressionNeuropsychopharmacology.  29:126-132. 2004
    2003 The combination of olanzapine and fluoxetine in mood disordersExpert Opinion on Pharmacotherapy.  4:1175-1183. 2003
    2003 The combination of olanzapine and fluoxetine in mood disorders.Expert Opinion on Pharmacotherapy.  4:1175-1183. 2003
    2003 The use of antidepressants in novel combination therapiesJournal of Clinical Psychiatry.  64:14-18. 2003
    2003 Treating bipolar depressionJournal of Family Practice.  52:14-17. 2003
    2002 St John's wort for the treatment of depressionLancet Neurology.  1:275. 2002
    2002 Noradrenergic antidepressants: Does chronic treatment increase or decrease nuclear CREB-P?Journal of Neural Transmission.  109:91-99. 2002
    2002 Mechanism of action of antidepressants.Psychopharmacology Bulletin.  36 Suppl 2:123-132. 2002
    2001 St John's wort was no better than placebo for reducing depression scoresEvidence Based Medicine.  6:185. 2001
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    2001 Antidepressant therapy: New targets for drug developmentExpert Opinion on Therapeutic Patents.  11:1693-1711. 2001
    2001 Can recovery from depression be achieved?Psychiatric Services.  52:1469-1478. 2001
    2001 Detection of an mRNA polymorphism by Differential DisplayMolecular Biotechnology.  19:121-124. 2001
    2001 Cross-talk between PKA and PKC in human fibroblasts: What are the pharmacotherapeutic implications?Journal of Affective Disorders.  65:275-279. 2001
    2001 Mechanisms of action in the treatment of anxietyJournal of Clinical Psychiatry.  62:10-15. 2001
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    2001 A novel augmentation strategy for treating resistant major depressionAmerican Journal of Psychiatry.  158:131-134. 2001
    2001 Do Dual-Action Neurotransmitter Agents Offer an Advantage in Psychiatric Treatment?CNS Spectrums.  6:1-8. 2001
    2001 Introduction: Remission of anxiety-related disordersJournal of Clinical Psychiatry.  62:3-4. 2001
    2001 Serum thyrotropin concentrations and bioactivity during sleep deprivation in depressionArchives of General Psychiatry.  58:77-83. 2001
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    2000 Chronic depression: Now, a treatable conditionPatient Care -Darien Connecticut then Montvale-.  34:56-66. 2000
    2000 Human fibroblasts as a relevant model to study signal transduction in affective disordersJournal of Affective Disorders.  61:51-58. 2000
    2000 Cellular mechanisms in the vulnerability to depression and response to antidepressantsPsychiatric Clinics of North America.  23:713-729. 2000
    2000 Intracellular mechanisms of antidepressant drug actionHarvard Review of Psychiatry.  8:161-174. 2000
    1999 The reliability and validity of a measure of self-understanding of interpersonal patternsJournal of Counseling Psychology.  46:472-482. 1999
    1999 Mood-stabilizing drugs in depressionJournal of Clinical Psychiatry.  60:37-42. 1999
    1999 Treatment options for refractory depressionJournal of Clinical Psychiatry.  60:57-63. 1999
    1999 Cyclic AMP-dependent protein kinase in subtypes of major depression and normal volunteersInternational Journal of Neuropsychopharmacology.  2:187-192. 1999
    1998 Update on the management of bipolar illnessJournal of Clinical Psychiatry.  59:484-495. 1998
    1997 Double-blind comparison of sertraline, imipramine, and placebo in the treatment of dysthymia: Psychosocial outcomesAmerican Journal of Psychiatry.  154:390-395. 1997
    1997 The undertreatment of dysthymiaJournal of Clinical Psychiatry.  58:59-65. 1997
    1996 cAMP-dependent protein kinase activity in major depressionAmerican Journal of Psychiatry.  153:1037-1042. 1996
    1996 β-Adrenoceptor-linked protein kinase A (PKA) activity in human fibroblasts from normal subjects and from patients with major depressionNeuropsychopharmacology.  15:555-561. 1996
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    1993 The effects of race and comorbidity on clinical diagnosis in patients with psychosisJournal of Clinical Psychiatry.  54:96-102. 1993
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    Chapter

    Year Title Altmetric
    2016 Anxiety disorders.  145-168. 2016
    2015 microRNAs as novel players in depression pathogenesis and in the mechanisms of action of fluoxetine and other antidepressants.  147-166. 2015
    2008 Anxiety disorders.  133-159. 2008

    Research Overview

  • Depression. Suicide. Bipolar disorder. Experimental therapeutics. Biomarker identification.
  • Principal Investigator On

  • Private Grant  awarded by ALLERGAN, INC. 2019 - 2024
  • Private Grant  awarded by NAVITOR PHARMACEUTICALS INC. 2019 - 2024
  • Private Grant  awarded by INTRA-CELLULAR THERAPIES INC. 2018 - 2023
  • Private Grant  awarded by OTSUKA PHARMACEUTICAL DEVELOPMENT & COMMERCIALIZATION, INC 2018 - 2022
  • Private Grant  awarded by ALLERGAN SALES, LLC 2017 - 2022
  • Private Grant  awarded by ALLERGAN SALES, LLC 2017 - 2022
  • Private Grant  awarded by ALLERGAN SALES, LLC 2017 - 2022
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2016 - 2022
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2016 - 2021
  • Private Grant  awarded by Janssen 2016 - 2021
  • Private Grant  awarded by Janssen 2016 - 2021
  • Private Grant  awarded by NEURORX 2017 - 2020
  • Augmentation Versus Switch: Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders with Treatment Resistant Depression (ASCERTAIN-TRD)  awarded by PATIENT CENTERED OUTCOMES RESEARCH INSTITUTE 2017 - 2020
  • Private Grant  awarded by NOVARTIS PHARMACEUTICALS CORPORATION - NEW 2019 - 2020
  • MicroRNA Mediators of Early Life Stress Vulnerability and Resilience  awarded by National Institute of Mental Health/NIH/DHHS 2017 - 2020
  • Private Grant  awarded by ACADIA PHARMACEUTICALS, INC. 2017 - 2020
  • Private Grant  awarded by ALLERGAN, INC. 2018 - 2020
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2017 - 2019
  • Private Grant  awarded by GENOMIND 2016 - 2019
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2015 - 2018
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2015 - 2018
  • A Placebo-Controlled, Crossover Study of Fanapt® (iloperidone) Augmentation of SSRIs for Residual Anger and Irritability in Major Depressive Disorder  awarded by MASSACHUSETTS GENERAL HOSPITAL 2013 - 2018
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2015 - 2018
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2015 - 2018
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2017 - 2018
  • Private Grant  awarded by ALLERGAN, INC. 2016 - 2018
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2015 - 2018
  • Private Grant  awarded by ALKERMES, INC. 2014 - 2017
  • Private Grant  awarded by FOREST LABORATORIES, INC. 2014 - 2017
  • Private Grant  awarded by NAUREX, INC. 2012 - 2017
  • Private Grant  awarded by NAUREX, INC. 2014 - 2017
  • Private Grant  awarded by ALKERMES, INC. 2014 - 2017
  • Private Grant  awarded by TAL MEDICAL 2013 - 2017
  • Rapidly-Acting Treatments for Treatment-Resistance Depression  awarded by MASSACHUSETTS GENERAL HOSPITAL 2012 - 2016
  • Private Grant  awarded by OTSUKA PHARMACEUTICAL DEVELOPMENT & COMMERCIALIZATION, INC 2012 - 2016
  • Double-Blind, Placebo-Controlled, Proof-of-Concept (POC) Trial of CERC-501, a Kappa-Selective Opioid Receptor Antagonist, Augmentation of Antidepressant Therapy in Treatment-Resistant Depression (TRD)  awarded by MASSACHUSETTS GENERAL HOSPITAL 2015 - 2016
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2014 - 2016
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2014 - 2015
  • Private Grant  awarded by ASSUREX HEALTH INC. 2014 - 2015
  • Private Grant  awarded by AVANIR PHARMACEUTICALS, INC. 2014 - 2015
  • Private Grant  awarded by TAKEDA GLOBAL RESEARCH & DEVELOPMENT CENTER 2012 - 2015
  • Private Grant  awarded by TAKEDA GLOBAL RESEARCH & DEVELOPMENT CENTER 2012 - 2015
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2012 - 2015
  • Private Grant  awarded by OTSUKA PHARMACEUTICAL DEVELOPMENT & COMMERCIALIZATION, INC 2013 - 2015
  • Private Grant  awarded by PAMLAB LLC 2014 - 2015
  • Assay of Inflammatory Cytokines, High Sensitivity C-Reactive Protein, Leptin, and Insulin in Plasma Samples of Outpatient Participants in L-Methylfolate (Deplin®) TRD-I and TRD-II Trials  awarded by MASSACHUSETTS GENERAL HOSPITAL 2013 - 2015
  • Paliperidone and Lithium in the Treatment of Suicidality - Treatment Indication and Epigenetic Regulation  awarded by American Foundation for Suicide Prevention 2012 - 2014
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2014
  • Private Grant  awarded by CERECOR, INC. 2013 - 2014
  • Private Grant  awarded by Janssen 2013 - 2014
  • Private Grant  awarded by Elan 2012 - 2014
  • 2/2- Ziprasidone Augmentation of SSRIs for Treatment-Resistant Depression  awarded by National Institute of Mental Health/NIH/DHHS 2012 - 2014
  • Private Grant  awarded by Janssen 2013 - 2014
  • Private Grant  awarded by JANSSEN RESEARCH & DEVELOPMENT, LLC 2012 - 2013
  • Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder  awarded by MASSACHUSETTS GENERAL HOSPITAL 2012 - 2013
  • Statistical Methods for Comparative Treatment Effectiveness Using Claims Data  awarded by VANDERBILT UNIVERSITY MEDICAL CENTER 2012 - 2013
  • Investigator On

  • Epitranscriptomic Mapping of Novel N6-Adenosine-based RNA Methylation in MDD Brain  awarded by National Institute of Mental Health/NIH/DHHS 2019 - 2024
  • Balanced Placebo Design with Varenicline: Pharmacological and Expectancy Effects on Medication Adherence  awarded by National Institute on Drug Abuse/NIH/DHHS 2018 - 2021
  • A Sleep and Media Intervention to Improve Adolescents Weight and Risk of Type 2 Diabetes  awarded by National Institute of Diabetes and Digestive and Kidney Diseases/NIH/DHHS 2016 - 2021
  • Structural and Neurometabolic White Matter Integrity in the Deficit Syndrome  awarded by National Institute of Mental Health/NIH/DHHS 2015 - 2020
  • NRT Sampling and Selection to Increase Medication Adherence  awarded by National Institute on Drug Abuse/NIH/DHHS 2017 - 2020
  • Plasma Exosomal MicroRNAs as Promising Novel Biomarkers for Suicidality and Treatment Outcome  awarded by National Institute of Mental Health/NIH/DHHS 2015 - 2020
  • Identification for Predictors of Future Diabetes - Impacts of Stress and Depression  awarded by National Institute of Diabetes and Digestive and Kidney Diseases/NIH/DHHS 2015 - 2019
  • Plasma MicroRNAs as Biomarker for Suicidality and Treatment Outcome  awarded by American Foundation for Suicide Prevention 2015 - 2018
  • Private Grant  awarded by ASSUREX HEALTH INC. 2016 - 2018
  • Private Grant  awarded by ASSUREX HEALTH INC. 2016
  • [18F] FPEB Studies of the mGluR5 Receptor and Methamphetamine Abuse  awarded by National Institute on Drug Abuse/NIH/DHHS 2014 - 2016
  • Glucose Metabolism and Insulin Sensitivity in Depressed Patients following Early Life Stress  awarded by Brain and Behavior Research Foundation 2014 - 2016
  • Training Interventions and Genetics of Exercise Response (TIGER)  awarded by University of Texas at Austin 2013 - 2015
  • Private Grant  awarded by INNOPHARMA, INC. 2013 - 2014
  • Education And Training

  • University of Louisville Hospital, Internship 1980
  • Harvard Medical School, Residency 1983
  • National Institute of Mental Health & Neuroscience, Postdoctoral Fellowship 1985
  • Full Name

  • Richard Shelton